Although effective and feasible means of reducing in-utero and intra-partum HIV transmission are now becoming available in resource-limited settings, prevention of post-partum transmission through breastfeeding remains a critical challenge. This study, now being conducted in collaboration with studies underway in Kampala, Uganda and Pune, India will evaluate the efficacy of a 6 week prophylactic regimen of nevirapine in the prevention of HIV transmission among breastfed infants. The primary endpoint is infant HIV infection status at 6 months of age. To date, 559 HIV seropositive women have been enrolled in this randomized, double-masked study with a 93% infant follow-up rate at 6 months of age. A total of 770 seropositive, breastfeeding women will be enrolled in Ethiopia. Enrollment will be completed in approximately 6-8 months with final follow-up of the women and their infants ending 12 months later. Breastfeeding among HIV-infected women continues to be supported in many resource poor settings because of the excess risk of morbidity and mortality associated with alternative feeding. However, at least one study has suggested that alternative feeding of infants born to HIV-infected women may not necessarily be associated with such increased risks. The study in Ethiopia is evaluating the risks associated with infant feeding practices by also enrolling and following two additional cohorts: non-breastfeeding HIV-infected woman and their infants and HIV negative women and their infants. Data from the randomized cohort study will assist in determining whether infant prophylaxis early in breastfeeding can significantly reduce post-partum transmission. As indicated above, feasible effective intervention strategies to prevent HIV transmission through breastfeeding are urgently needed. The data regarding morbidity and mortality rates by feeding modality will inform future policy decisions addressing the risks and benefits of a given feeding practice for HIV-infected women.